Gli3 Recombinant Rabbit Monoclonal Antibody [JG83-39]

Function

Zinc-finger proteins contain DNA-binding domains and have a wide variety of functions, most of which encompass some form of transcriptional activation or repression. The majority of zinc-finger proteins contain a Krüppel-type DNA binding domain and a KRAB domain, which is thought to interact with KAP1, thereby recruiting histone modifying proteins. GLI-3 (GLI family zinc finger 3), also known as GLI3FL (GLI3 full length protein), PHS, ACLS, GCPS, PAPA, PAPB, PAPA1 or PPDIV, is a 1,580 amino acid nuclear and cytoplasmic protein that acts as both a transcriptional activator and a repressor of the Sonic hedgehog (Shh) pathway. A member of the GLI C2H2-type zinc-finger protein family, GLI-3 is encoded by a gene that maps to human chromosome 7p14.1. Defects in the GLI-3 gene are the cause of a disorder known as Greig cephalo-poly-syndactyly syndrome (GCPS), which affects limb and craniofacial development.

Background References

1. Wang B et al. Hedgehog-regulated processing of Gli3 produces an anterior/posterior repressor gradient in the developing vertebrate limb. Cell 100:423-434 (2000).

2. Koyabu Y et al. Physical and functional interactions between Zic and Gli proteins. J Biol Chem 276:6889-6892 (2001).

Sequence Similarity

Belongs to the GLI C2H2-type zinc-finger protein family.

Tissue Specificity

Is expressed in a wide variety of normal adult tissues, including lung, colon, spleen, placenta, testis, and myometrium.

Post-translational Modification

Phosphorylated on multiple sites by protein kinase A (PKA) and phosphorylation by PKA primes further phosphorylation by CK1 and GSK3. Phosphorylated by DYRK2 (in vitro). Phosphorylation is essential for its proteolytic processing.; Transcriptional repressor GLI3R, a C-terminally truncated form, is generated from the full-length GLI3 protein (GLI3FL/GLI3-190) through proteolytic processing. This process requires PKA-primed phosphorylation of GLI3, ubiquitination of GLI3 and the presence of BTRC. GLI3FL is complexed with SUFU in the cytoplasm and is maintained in a neutral state. Without the Hh signal, the SUFU-GLI3 complex is recruited to cilia, leading to the efficient processing of GLI3FL into GLI3R. GLI3R formation leads to its dissociation from SUFU, allowing it to translocate into the nucleus, and repress Hh target genes. When Hh signaling is initiated, SUFU dissociates from GLI3FL and this has two consequences. First, GLI3R production is halted. Second, free GLI3FL translocates to the nucleus, where it is phosphorylated, destabilized, and converted to a transcriptional activator (GLI3A). Phosphorylated in vitro by ULK3.

Subcellular Location

Cytoplasm. Nucleus.

UNIPROT

SwissProt: P10071 Human

Synonyms